IL-13 enhances mesenchymal transition of pulmonary artery endothelial cells via down-regulation of miR-424/503 in vitro

Cell Signal. 2018 Jan;42:270-280. doi: 10.1016/j.cellsig.2017.10.019. Epub 2017 Nov 2.

Abstract

Pulmonary arterial hypertension (PAH) has a major effect on life expectancy with functional degeneracy of the lungs and right heart. Interleukin-13 (IL-13), one of the type 2 cytokines mainly associated with allergic diseases, has recently been reported to be associated with Schistosomiasis-associated PAH which shares pathological features with other forms of PAH, such as idiopathic PAH and connective tissue disease-associated PAH. But a direct pathological role of IL-13 in the development of PAH has not been explored. We examined the effects of recombinant human IL-13 on the function of primary human pulmonary artery endothelial cells (HPAECs) to examine how IL-13 influences exacerbation of PAH. IL-13 increased the expression of Rictor, which is a key molecule of mammalian target of rapamycin complex 2. Treatment of IL-13 induced HPAEC migration via Rictor. Rictor was directly regulated by both miR-424 and 503 (miR-424/503). Therefore, IL-13 increases Rictor level by regulating miR-424/503, causing the increase of HPAEC migration. Since enhancement of HPAEC migration in the lung is thought to be associated with PAH, these data suggest that IL-13 takes some roles in exacerbating PAH.

Keywords: Histone deacetylase (HDAC); Interleukin 13 (IL-13); MicroRNA-424/503; Pulmonary arterial hypertension (PAH); Rictor.

MeSH terms

  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation
  • Humans
  • Hypertension, Pulmonary / genetics
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / physiopathology
  • Interleukin-13 / pharmacology*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Biological
  • Primary Cell Culture
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • Rapamycin-Insensitive Companion of mTOR Protein / genetics*
  • Rapamycin-Insensitive Companion of mTOR Protein / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction

Substances

  • IL13 protein, human
  • Interleukin-13
  • MIRN424 microrna, human
  • MIRN503 microRNA, human
  • MicroRNAs
  • RICTOR protein, human
  • Rapamycin-Insensitive Companion of mTOR Protein
  • Recombinant Proteins